Chemoenzymatic enantiodivergent total syntheses of (+)- and (−)-codeine

Utilization of Volatile Organic Compounds as an Alternative for Destructive Abatement

“…Ethyl ether is used as anesthetic, and codeine is the methyl ether of morphine [293,294]. Codeine can be produced also from diols via chemoenzymatic synthesis [295]. Dimethyl ether is used as a propellant and methyl t-butyl ether (MTBE) is used as octane number increasing additive in gasoline [296].…”

Response Surface Methodology Optimization of Thebaine Biotransformation into Codeine and Morphine Using Bacillus sp. FAR

“…2-9-18 The World Drug Report of 2015 on narcotic drugs states that global opium production reached 7554 tons in 2014 and worldwide consumption is increasing. Because of illicite use, cultivation of the opium poppy continues 4 therefore, it is necessary to find other sources for morphine and codeine [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] The non-narcotic thebaine, the main alkaloid of P. bracteatum, 20 has been a focus of attention because it accumulates thebaine with no morphine and codeine. 21 Thebaine is an excellent starting material for synthesis of diverse morphine agonists and antagonists.…”

“…In recent years, microbial production of secondary plant metabolites as an alternative method of synthesis of such effective compounds has been of increased interest. [10][11][12][13][14][15][16][17][18] Microbial transformation is the modification of certain compounds by enzymatic reactions 22 to achieve specific and useful metabolite accumulation through environmentally harmless and simpler bioprocesses. 23 Selecting microbial reactions directed toward the native plant hosts as alternative to chemical synthesis employed in traditional methods offers benefits such as quick accumulation of biomass, production of main intermediate molecules separately, simplicity of purification and accessibility of genetic tools for additional optimization.…”

Chemoenzymatic Formal Total Synthesis of ent‐Codeine and Other Morphinans via Nitrone Cycloadditions and/or Radical Cyclizations. Comparison of Strategies for Control of C‐9/C‐14 Stereogenic Centers

“…[3] The authors of most of the synthetic strategies understand that the stereochemistry of the C-5 center, if established early, controls the subsequent stereochemical events and can therefore be exploited in enantiodivergent design, as illustrated in some of our recent papers. [4] One of the challenges in any design of the morphine skeleton is the relative stereochemistry at C-9/ C-14 -this can be controlled by employing cycloadditions. In 1984 Parsons published a model study of an intramolecular nitrone cycloaddition, which produced the correct C-9/C-14 relationship, [5] followed by a complete total synthesis of morphine by this strategy.…”

“…Synthesis of ent-codeinone and ent-codeine via nitrone cycloaddition. i) E. coli JM109 (pDTG601A), 5 g L À1 ; ii) potassium azodicarboxylate (PAD), HOAc, MeOH, 84%; iii) TBSCl, imidazole, DMF, 54%; iv) DIAD, (n-Bu) 3 P, THF, phenol 9, 79.5%; v) PdA C H T U N G T R E N N U N G (dba) 2 , K 2 CO 3 , (t-Bu) 3 P, toluene, reflux, 64%; vi) 50% aqueous TFA, toluene, 50 8C, 92%; vii) NHMeOH·HCl, Hünigs base, toluene, reflux, 38%; viii) Meerwein salt, CH 2 Cl 2 , then LiAlH 4 , THF, 76% over 2 steps; ix) Dess-Martin periodinane, CH 2 Cl 2 , 75%; x) NH 2 Me·HCl, NEt 3 ,TiA C H T U N G T R E N N U N G (i-PrO) 4 , MeOH, then NaBH 4 ; xi) BOC anhydride, EtOH, 66% over 3 steps; xii) TBAF, THF; xiii. Dess-Martin Periodinane, CH 2 Cl 2 , 51% over 2 steps.…”